Lysosome-associated membrane protein 2 (LAMP-2, also known as CD107b) is a gene that encodes a lysosome-associated membrane glycoprotein. Alternative splicing of the gene produces three isoforms: LAMP-2A, LAMP-2B, and LAMP-2C. Loss-of-function mutations in LAMP-2 are associated with human diseases, including Danon disease, a familial cardiomyopathy associated with impaired autophagy.
International Patent Application Publication No. WO2017127565A1 discloses that overexpression of LAMP-2 in human induced pluripotent stem cells (hiPSCs) derived from patients with LAMP-2 mutations, as described in Hashem, et al., Stem Cells. 2015 July; 33(7):2343-50, results in reduced oxidative stress levels and apoptotic cell death, confirming the importance of LAMP-2B in disease pathophysiology.
There remains a need in the art for gene therapy vectors for LAMP-2. The present disclosure provides such gene therapy vectors, methods of use thereof, pharmaceutical compositions, and more.